Modulating the site-specific oral delivery of sorafenib using sugar-grafted nanoparticles for hepatocellular carcinoma treatment

Eur J Pharm Sci. 2019 Sep 1:137:104978. doi: 10.1016/j.ejps.2019.104978. Epub 2019 Jun 26.

Abstract

Globally, one in six deaths is reported due to cancer suggesting the critical need for development of advanced treatment regimens. In this study, solid lipid nanoparticles (SLN) were prepared and appended with polyethylene glycol (PEGylated) galactose and a multikinase inhibitor sorafenib (SRFB) was used as chemotherapeutic drug, for treating hepatocellular carcinoma (HCC). The nanoparticles were evaluated for in-vitro and in-vivo performances to showcase the targeting efficiency and therapeutic benefits of the sorafenib loaded ligand conjugated nanoparticles (GAL-SSLN). When compared with SRFB or Sorafenib loaded SLN, GAL-SSLN showed superior cytotoxicity and apoptosis in HepG2 (human hepatocellular carcinoma cells). In addition, in-vivo pharmacokinetics and real time biodistribution studies in BALB/c mice showed that the surface conjugation of nanoparticles with galactose resulted in better pharmacokinetic performance and targeted delivery of the nanoparticles to liver. Results indicated that GAL-SSLN showed promising attributes in terms of targeting sorafenib to liver and therapeutic efficacy.

Keywords: Bioavailability; Hepatocellular carcinoma; PEGylated galactose; Solid lipid nanoparticles; Sorafenib; Targeting.

MeSH terms

  • Administration, Oral
  • Animals
  • Antineoplastic Agents / administration & dosage*
  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / pharmacokinetics
  • Carcinoma, Hepatocellular / drug therapy*
  • Cell Proliferation / drug effects
  • Drug Liberation
  • Galactose / administration & dosage*
  • Galactose / chemistry
  • Galactose / pharmacokinetics
  • Hep G2 Cells
  • Humans
  • Lipids / administration & dosage
  • Lipids / chemistry
  • Lipids / pharmacokinetics
  • Liver Neoplasms / drug therapy*
  • Membrane Potential, Mitochondrial / drug effects
  • Mice, Inbred BALB C
  • Nanoparticles / administration & dosage*
  • Nanoparticles / chemistry
  • Polyethylene Glycols / administration & dosage
  • Polyethylene Glycols / chemistry
  • Sorafenib / administration & dosage*
  • Sorafenib / chemistry
  • Sorafenib / pharmacokinetics
  • Tissue Distribution

Substances

  • Antineoplastic Agents
  • Lipids
  • Polyethylene Glycols
  • Sorafenib
  • Galactose